The aim of this longitudinal study was to assess the frequency of nonreversible airflow obstruction (NRAO) among adults with moderate to severe asthma, and to compare the decline of forced expiratory volume in one second (FEV1) in asthmatics with reversible and nonreversible airflow obstruction. Ninety-two (31 males) life-long nonsmokers with asthma participated in a 10-yr follow-up study; mean age 37 yrs (range 18-64) and duration of asthma 16 yrs (range 2-60) at enrolment. Case history, including use of asthma medication, was obtained, and pulmonary function, including diffusion capacity, was measured using standard techniques. At enrolment, all patients had typical symptoms and reversible airflow obstruction. (NRAO) was defined as FEV1 <80% predicted and change in deltaFEV1 after 5 mg salbutamol <9% pred. A total of 21 (23%) patients (mean age at enrolment 32 yrs) fulfilled the criteria for NRAO at the time of follow-up; current therapy was inhaled steroids (n=21, mean daily dose 1.5 mg), oral steroids (n=14), theophylline (n=20), oral beta2-agonist (n=6) and inhaled beta2-agonist. The patients with NRAO (n=21) had a steeper decline in FEV1 than the remaining patients (n=71, reversible airflow obstruction (RAO)), mean+/-SD 53+/-23 mL x yr(-1) and 36+/-21 mL x yr(-1), respectively (p<0.003). Increasing degree of bronchodilator reversibility (deltaFEV1% pred) at enrolment (p=0.002) and long-term treatment with oral corticosteroids (p=0.009) were associated with an increased risk for the presence of NRAO at follow-up. The comparison of data for NRAO and RAO patients (at follow-up) revealed no significant differences in mean values for total diffusion capacity (TL,CO), diffusion constant (KCO), or total lung capacity. The findings suggest that a subgroup of asthmatics may experience very steep rates of decline in forced expiratory volume in one second leading to severe nonreversible airflow obstruction, whereas no indication was found that long-standing asthma may lead to the development of emphysema.